Emerging executive functioning and motor development in infants at high and low risk for autism spectrum disorder

Existing evidence suggests executive functioning (EF) deficits may be present in children with autism spectrum disorder (ASD) by 3 years of age. It is less clear when, prior to 3 years, EF deficits may emerge and how EF unfold over time. The contribution of motor skill difficulties to poorer EF in children with ASD has not been systematically studied. We investigated the developmental trajectory of EF in infants at high and low familial risk for ASD (HR and LR) and the potential associations between motor skills, diagnostic group, and EF performance. Participants included 186 HR and 76 LR infants. EF (A-not-B), motor skills (Fine and Gross Motor), and cognitive ability were directly assessed at 12 months and 24 months of age. Participants were directly evaluated for ASD at 24 months using DSM-IV-TR criteria and categorized as HR-ASD, HR-Negative, and LR-Negative. HR-ASD and HR-Negative siblings demonstrated less improvement in EF over time compared to the LR-Negative group. Motor skills were associated with group and EF performance at 12 months. No group differences were found at 12 months, but at 24 months, the HR-ASD and HR-Negative groups performed worse than the LR-Negative group overall after controlling for visual reception and maternal education. On reversal trials, the HR-ASD group performed worse than the LR-Negative group. Motor skills were associated with group and EF performance on reversal trials at 24 months. Findings suggest that HR siblings demonstrate altered EF development and that motor skills may play an important role in this process

Homogeneous Subgroups of Young Children with Autism Improve Phenotypic Characterization in the Study to Explore Early Development

The objective of this study was to identify homogenous classes of young children with autism spectrum disorder (ASD) to improve phenotypic characterization. Children were enrolled in the Study to Explore Early Development between 2 and 5 years of age. 707 children were classified with ASD after a comprehensive evaluation with strict diagnostic algorithms. Four classes of children with ASD were identified from latent class analysis: mild language delay with cognitive rigidity, mild language and motor delay with dysregulation, general developmental delay, and significant developmental delay with repetitive motor behaviors. We conclude that a four-class phenotypic model of children with ASD best describes our data and improves phenotypic characterization of young children with ASD. Implications for screening, diagnosis, and research are discussed

Friend matters: sex differences in social language during autism diagnostic interviews

Background: Autistic individuals frequently experience social communication challenges. Girls are diagnosed with autism less often than boys even when their symptoms are equally severe, which may be due to insufficient understanding of the way autism manifests in girls. Differences in the behavioral presentation of autism, including how people talk about social topics, could contribute to these persistent problems with identification. Despite a growing body of research suggesting that autistic girls and boys present distinct symptom profiles in a variety of domains, including social attention, friendships, social motivation, and language, differences in the way that autistic boys and girls communicate verbally are not yet well understood. Closely analyzing boys’ and girls’ socially-focused language during semi-structured clinical assessments could shed light on potential sex differences in the behavioral presentation of autistic individuals that may prove useful for identifying and effectively supporting autistic girls. Here, we compare social word use in verbally fluent autistic girls and boys during the interview sections of the ADOS-2 Module 3 and measure associations with clinical phenotype. Methods: School-aged girls and boys with autism (N = 101, 25 females; aged 6–15) were matched on age, IQ, and parent/clinician ratings of autism symptom severity. Our primary analysis compared the number of social words produced by autistic boys and girls (normalized to account for differences in total word production). Social words are words that make reference to other people, including friends and family. Results: There was a significant main effect of sex on social word production, such that autistic girls used more social words than autistic boys. To identify the specific types of words driving this effect, additional subcategories of friend and family words were analyzed. There was a significant effect of sex on friend words, with girls using significantly more friend words than boys. However, there was no significant main effect of sex on family words, suggesting that sex differences in social word production may be driven by girls talking more about friends compared to boys, not family. To assess relationships between word use and clinical phenotype, we modeled ADOS-2 Social Affect (SA) scores as a function of social word production. In the overall sample, social word use correlated significantly with ADOS-2 SA scores, indicating that participants who used more social words were rated as less socially impaired by clinicians. However, when examined in each sex separately, this result only held for boys. Limitations: This study cannot speak to the ways in which social word use may differ for younger children, adults, or individuals who are not verbally fluent; in addition, there were more autistic boys than girls in our sample, making it difficult to detect small effects. Conclusions: Autistic girls used significantly more social words than boys during a diagnostic assessment—despite being matched on age, IQ, and both parent- and clinician-rated autism symptom severity. Sex differences in linguistic markers of social phenotype in autism are especially important in light of the late or missed diagnoses that disproportionately affect autistic girls. Specifically, heightened talk about social topics could complicate autism referral and diagnosis when non-clinician observers expect a male-typical pattern of reduced social focus, which autistic girls may not always exhibit

Early brain development in infants at high risk for autism spectrum disorder

Brain enlargement has been observed in children with Autism Spectrum Disorder (ASD), but the timing of this phenomenon and its relationship to the appearance of behavioral symptoms is unknown. Retrospective head circumference and longitudinal brain volume studies of 2 year olds followed up at age 4 years, have provided evidence that increased brain volume may emerge early in development.1, 2 Studies of infants at high familial risk for autism can provide insight into the early development of autism and have found that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life3,4. These observations suggest that prospective brain imaging studies of infants at high familial risk for ASD might identify early post-natal changes in brain volume occurring before the emergence of an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that cortical surface area hyper-expansion between 6-12 months of age precedes brain volume overgrowth observed between 12-24 months in the 15 high-risk infants diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep learning algorithm primarily using surface area information from brain MRI at 6 and 12 months of age predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81%, sensitivity of 88%). These findings demonstrate that early brain changes unfold during the period in which autistic behaviors are first emerging

The Modified Checklist for Autism in Toddlers (M-CHAT) sibling study: Are younger siblings representative of the general ASD population?

Research indicates that younger siblings of children with autism are at higher risk for the development of autism and other developmental disorders (Silverman, 2001). As a result, many researchers have focused on younger siblings as a way of studying the emergence of autism prospectively. While this research has yielded many interesting findings, it is not known whether siblings are representative of singleton cases of autism spectrum disorders (ASD).^ The current study used the M-CHAT (Robins, et al., 2001), a parent-report checklist, to detect ASD in 16–30 month old younger siblings of ASD probands. Three cohorts of children were compared: multiplex/younger siblings, an early intervention/high-risk singleton sample (EI), and a pediatrician screened/low-risk singleton sample (Peds). Two hundred and thirteen younger siblings, 583 EI toddlers, and 4281 Peds toddlers have been screened, with a mean age of 20 months for each group. Ninety-six younger siblings failed the screening and 78 of these also failed the telephone interview follow-up, and qualified for a developmental evaluation (mean age 23 months). Forty-eight of these siblings have been diagnosed with ASD, suggesting a recurrence rate of 22.5% in our sibling sample, with an ASD recurrence rate of 25% in our University of Connecticut sample and 21% in our University of Washington Sample. ^ With regards to severity of autism, our ASD sibling sample was similar to our singleton ASD sample on all diagnostic variables. However, our ASD sibling sample was higher functioning than our singleton ASD sample in adaptive skills (Vineland Socialization) and cognitive development (Mullen Visual Reception, Fine Motor, and Expressive Language). Although ascertainment bias may play a role in these differences, the data suggest that autism in multiplex families may be different from autism in singleton families and that caution is warranted when generalizing from development of affected younger siblings to development of autism in general.

The Modified Checklist for Autism in Toddlers (M-CHAT) sibling study: Are younger siblings representative of the general ASD population?

Research indicates that younger siblings of children with autism are at higher risk for the development of autism and other developmental disorders (Silverman, 2001). As a result, many researchers have focused on younger siblings as a way of studying the emergence of autism prospectively. While this research has yielded many interesting findings, it is not known whether siblings are representative of singleton cases of autism spectrum disorders (ASD).^ The current study used the M-CHAT (Robins, et al., 2001), a parent-report checklist, to detect ASD in 16–30 month old younger siblings of ASD probands. Three cohorts of children were compared: multiplex/younger siblings, an early intervention/high-risk singleton sample (EI), and a pediatrician screened/low-risk singleton sample (Peds). Two hundred and thirteen younger siblings, 583 EI toddlers, and 4281 Peds toddlers have been screened, with a mean age of 20 months for each group. Ninety-six younger siblings failed the screening and 78 of these also failed the telephone interview follow-up, and qualified for a developmental evaluation (mean age 23 months). Forty-eight of these siblings have been diagnosed with ASD, suggesting a recurrence rate of 22.5% in our sibling sample, with an ASD recurrence rate of 25% in our University of Connecticut sample and 21% in our University of Washington Sample. ^ With regards to severity of autism, our ASD sibling sample was similar to our singleton ASD sample on all diagnostic variables. However, our ASD sibling sample was higher functioning than our singleton ASD sample in adaptive skills (Vineland Socialization) and cognitive development (Mullen Visual Reception, Fine Motor, and Expressive Language). Although ascertainment bias may play a role in these differences, the data suggest that autism in multiplex families may be different from autism in singleton families and that caution is warranted when generalizing from development of affected younger siblings to development of autism in general.